The continuing objectives of this project are to characterize the functions of cells in the murine immune system and determine the mechanisms of interactions among these cells operative in the generation and regulation of antibody responses in tissue culture systems. These experiments will focus on genetic restrictions imposed by products of the I region of the H-2 gene complex which govern macrophage-immune T cell interactions in antibody responses. The generality of these phenomena observed in the GAT system will be probed using other antigens, such as fowl gamma globulin and TGAL, to compare in detail similarities and differencies in genetic restrictions governing responses to these antigens. The contribution of antigen-specific suppressor T cells to the genetic restrictions governing macrophage-immune helper T cell interactions will be studied to determine if the helper T cells themselves are restricted or whether the suppressor T cells dictate the activity of helper T cells. Experiments to investigate the mechanism(s) by which these antigen-specific suppressor T cells function in primary and secondary responses will be undertaken. To further compare helper and suppressor T cells, we will investigate the conditions which favor activation of helper versus suppressor cells in vivo and in vitro. Lastly, the contribution of nonresponder Ir gene products in responses of immune (responder x nonresponder) F1 T cells to the antigen pulsed parental macrophages will be probed to test the hypothesis that functional allelic exclusion of Ir gene expression occurs in subsets of F1 T cells. These studies will include positive and negative selection procedures to obtain helper and suppressor T cells restricted for parental responder and nonresponder macrophages. These studies should contribute to the understanding of fundamental mechanisms regulating generation and expression of immune responses by defining the interrelationships among the functions of helper and suppressor T cells, Ir genes and I region products which impose restrictions on macrophage-T cell interactions in antibody responses.